WO2019092748A1

WO2019092748A1 - A nano fiber based osteo-conductive resorbable patch for bone regeneration

Info

Publication number: WO2019092748A1
Application number: PCT/IN2018/050732
Authority: WO
Inventors: Ghanshyam Das Agrawal
Original assignee: Ghanshyam Das Agrawal
Priority date: 2017-11-13
Filing date: 2018-11-12
Publication date: 2019-05-16

Abstract

This invention is directed to a nano fiber based osteo-conductive resorbable patch for bone regeneration comprising of Calcium phosphate salt, Strontium salt and Cupric salt. It is associated with the following advantageous features:- - Acts as medium for breeding/anchoring of osteoblasts - Forms a minute honeycomb structure for proliferation of osteoblasts - Beta TCP /HA acts as osteoconductive material, which conducts bone formation by virtue of calcium and phosphate ions. - Strontium limits activity of osteoclasts, thereby increasing bone formation speed. - Copper helps in formation of blood vessels, thereby further aiding bone formation activity. It has been used in several children to repair cranial defects and found to be highly successful. It has also been implemented in detail segment for many purposes.

Description

A nano fiber based osteo-conductive resorbable patch for bone regeneration

FIELD OF INVENTION

[001] This invention relates to a nano fiber based osteo-conductive resorbable patch for bone regeneration. The patch can be employed to treat/ repair hollow bone defects and to contain stabilize bone fragments for better bone healing.

BACKGROUND /PRIOR ART OF INVENTION

[002] Following accidents of head, tumor surgery involving bone of skull, bone of the skull is lost & cranial defects are formed. There are several methods to repair the cranial defects, which can be discussed hereinunder.

[003] Oldest & commonest one is to use Titanium mesh. A mesh of titanium is cut and shaped manually, which is fixed on the skull with the help of screws.

[004] Another method is to print 3D model of the cranial flap using a biocompatible material such as PMMA, PEEK and titanium powder, wherein CT scan data of the patient is used to create the model. After sterilization the 3D printed cranial flap is implanted on the skull.

[005] Another method involves 3D printing of the flap using Calcium phosphate in form of Hydroxyapatite, in which Hydroxyapatite forms a mineral our bones are made thereof.

l [006] However, the above methods are associated with several disadvantages as follows: -

1. Titanium mesh has its own problems with sharp edges and pointed sharp projections, which injure the overlying skin. Many times mesh protrude out.

2. All the methods described above use hard material to make a cranial flap. In children and upto the age of 18 years, hard material can't be used so as to repair the cranial or any other bony defects. The skull grows upto 18 years and the hard implant used to repair the skull does not grow. This restricts growth of head and causes deformation of skull, thereby restricting growth of brain inside the skull.

3. An implant is an implant, always a foreign body among body tissues, howsoever biocompatible and good it may be. It is always prone to get rejected, infected and cause many other discomforts.

[007] Electrospinning of nano fibers is known for several decades. Faster electrospinning machines are recent phenomena. Similarly electrospinning of resorbable polymers is well established. Many polymers such as Poly lactic acid, poly caprolactone, poly glycolic acid & their combinations have been used to make electrospun nanofiber sheets.

[008] However, the aforesaid nano fibers is useful for regeneration of soft tissues. The same can't be implemented for forming bone. [009] Thus, none of the above can serve the purpose, for which the present invention has been devised.

[0010] In view of the above, the present invention introduces a nano fiber based osteo-conductive resorbable patch for bone regeneration which is very effective and useful for treating hollow bone defects.

OBJECTS OF THE INVENTION

[0011] An object of this invention is to propose a nano fiber based osteo conductive resorbable patch for bone regeneration.

[0012] Another object of this invention is to propose an osteo- conductive patch for use in children and older patients for treatment of hollow bone defects.

[0013] Still another object of this invention is to propose an osteo- conductive patch which is soft.

[0014] Still another object of this invention is to propose an osteo- conductive patch which can be stitched around the bony defect.

[0015] Still another object of this invention is to propose an osteo- conductive patch which inhibits actions of osteoclasts to speedup bone healing.

[0016] Still another object of this invention is to propose an osteo- conductive patch to promote new vessel formation to speedup bone healing. [0017] Still another object of this invention is to propose an osteoinductive patch which is resorbable.

SUMMARY OF THE INVENTION

[0018] According to the invention, there is provided a nano fiber based osteo-conductive resorbable patch for bone regeneration comprising of 20-40% of Calcium phosphate salt, 2-5% of Strontium salt and 0.2-0.5% of Cupric salt.

[0019] The Calcium phosphate salt includes Beta tri calcium phosphate, Nano crystalline Hydroxyapatite and Bi calcium phosphate, the Strontium salt includes Strontium phosphate and the Cupric salt comprises Cupric chloride.

[0020] A process for preparation of nano fiber based osteo- conductive resorbable patch for bone regeneration comprising steps of:

- Preparation of a solution of bioresorbable polymer in a solvent,

- Addition of calcium phosphate salt to the solution with Strontium salt and Cupric salt so as to obtain a solution with suspension,

- Electrospinning of nanofibers deposited on a substrate to prepare the patch.

[0021] The bioresorbable polymer includes Polycaprolactone, Poly tetra methylene chloride (PTMC), Poly lactic acid, poly glycolic acid. [0022] The solvent includes a group of Halogenated solvents comprising of Chloroform, Tetrachloro methane, Dichloro methane.

[0023] The temperature during the process is 18-24°C. [0024] The patch, thickness of which ranges from 0. 1-25 mm.

[0025] The patch is applicable for repair of hollow bone defect such as cranium, maxillary sinus, spinal canal & palate etc. and containment of bone fragments, beta TCP / HA fillings.

DETAIL DESCRIPTION OF THE PRESENT INVENTION

[0026] The instant invention makes a disclosure regarding a technology pertaining to a nano fiber based osteo-conductive resorbable patch for bone regeneration.

[0027] The nano fiber based osteo-conductive resorbable patch is composed of salt of Calcium Phosphate, Strontium compound and Cupric compound.

[0028] The salt of Calcium Phosphate includes Beta tri calcium phosphate, Nano crystalline hydroxyapatite (3.6 calcium phosphate) and Bi calcium phosphate.

[0029]

[0030] The Calcium and Phosphate ions form basic building blocks of bone. Here, Beta TCP is the most preferred form of Calcium Phosphates for body implants. [0031] The Strontium compound includes Strontium phosphate that is required to slow down osteoclasts activity. There are two types of cells for bone activity in the body namely, osteoblasts and osteoclasts. Osteoblasts make bone and osteoclasts remove bone. In case osteoclast activity will be limited, the speed of bone formation will increase.

[0032] The Cupric compound comprises Cupric chloride. In this, Copper helps in formation of new blood vessels, thereby aiding formation of new bone.

[001] Thus, ions of Calcium Phosphate, Strontium and Copper are essentially needed so as to build the bone. Hence, any suitable salt of these ions apart from the ones mentioned hereinabove readily apparent to a person skilled in the art are understood to be within purview of the invention which may be adopted in order to achieve the same effect.

[0033] The composition of the resorbable patch is as follows: Salt of Calcium phosphate

(for example: Beta TCP) - 20-40%

Salt of Strontium

(for example: Strontium phosphate) - 2-5%

Salt of Copper

(for example: Cupric chloride) - 0.2-0.5%

[0034] The process for preparation of a nano fiber based osteo- conductive resorbable patch for bone regeneration is described hereinbelow. [0035] A solution of Polycaprolactone in a suitable solvent is prepared. The solvent includes a group of Halogenated solvents comprising of Chloroform, Tetrachloro methane, Dichloro methane.

[0036] In place of Polycaprolactone, any bioresorbable polymer such as Poly tetra methylen chloride (PTMC), Poly lactic acid, poly glycolic acid can be employed.

[0037] Finely powdered beta tri calcium phosphate is added to the solution thus obtained with strontium carbonate & doped with cupric chloride. This solution with suspension is used to electrospun nanofibers deposited on a substrate so as to prepare thick patch/ sheet of these fibers.

[0038] The temperature maintained during the process is just air- conditioned temperature ranging from 18-24°C.

[0039] Thus, the instant invention results in a patch comprising of electorspun polycaprolactone combined with Beta tri calcium phosphate together with strontium carbonate doped with cupric chloride.

[0040] Different thickness of fabric/ patch are required for different purposes. Small patches are employed in thinner form and large patches for cranial defect repair are implemented in thicker forms. The thickness of patch can range from 0. 1 mm to 2.5 mm. Working Example

[0041] In 100 g of chloroform 7g of polycaprolactone is dissolved. 2.65 gram of nano crystalline beta tri calcium phosphate and 0.3 gm of strontium carbonate is added. It is doped with 50 mg of cupric chloride. This solution-suspension is elctrospun to make a fabric patch.

[0042] Advantageous Features associated with the present invention can be listed hereinunder:

- Acts as medium for breeding/ anchoring of osteoblasts

- Forms a minute honeycomb structure for proliferation of osteoblasts

- Beta TCP /HA acts as osteoconductive material, which conducts bone formation by virtue of calcium and phosphate ions.

- Strontium limits activity of osteoclasts, thereby increasing bone formation speed.

- Copper helps in formation of blood vessels, thereby further aiding bone formation activity.

Test Result

[0043] It has been used in several children to repair cranial defects and found to be highly successful. It has also been implemented in detail segment for many purposes.

Applications

- Repair of hollow bone defect such as cranium, maxillary sinus, spinal canal & palate etc.

- Containment of bone fragments, beta TCP / HA fillings. [0044] This invention proved to be very useful as nothing is available for repair of skull defects of children under the age of 18 years. Under 18 the brain and skull grows.

[0045] It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as "open" terms (e.g., the term "including" should be interpreted as "including but not limited to," the term "having" should be interpreted as "having at least," the term "includes" should be interpreted as "includes but is not limited to," etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases "at least one" and "one or more" to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles "a" or "an" limits any particulars claim containing such introduced claim recitation to inventions containing only one such recitation, even when the same claim includes the introductory phrases "one or more" or "at least one" and indefinite articles such as "a" or "an" (e.g., "a" and/ or "an" should typically be interpreted to mean "at least one" or "one or more"); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number (e.g., the bare recitation of "two recitations," without other modifiers, typically means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogues to "at least one of A, B and C, etc." is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., "a system having at least one of A, B and C" would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to "at least one of A, B, or C, etc." is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., "a system having at least one of A, B, or C" would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and/ or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase "A or B" will be understood to include the possibilities of "A" or "B" or "A and B".

[0046] It is to be noted that the present invention is susceptible to modifications, adaptations and changes by those skilled in the art. Such variant embodiments employing the concepts and features of this invention are intended to be within the scope of the present invention, which is further set forth under the following claims: -

Claims

I CLAIM:

1. A nano fiber based osteo-conductive resorbable patch for bone regeneration comprising of 20-40% of Calcium phosphate salt, 2-5% of Strontium salt and 0.2-0.5% of Cupric salt.

2. The nano fiber based osteo-conductive resorbable patch for bone regeneration as claimed in claim 1, wherein the Calcium phosphate salt includes Beta tri calcium phosphate, Nano crystalline Hydroxyapatite and Bi calcium phosphate, the Strontium salt includes Strontium phosphate and the Cupric salt comprises Cupric chloride.

3. The process for preparation of nano fiber based osteo- conductive resorbable patch for bone regeneration as claimed in any of the preceding claims, wherein the patch, thickness of which ranges from 0.1-2.5 mm.

4. A process for preparation of nano fiber based osteo- conductive resorbable patch for bone regeneration comprising steps of:

- Preparation of a solution of bioresorbable polymer in a solvent,

- Electrospinning of nanofibers deposited on a substrate to prepare the patch. The process for preparation of nano fiber based osteo- conductive resorbable patch for bone regeneration as claimed in claim 4, wherein the bioresorbable polymer includes Polycaprolactone, Poly tetra methylene chloride (PTMC), Poly lactic acid, poly glycolic acid.

The process for preparation of nano fiber based osteo- conductive resorbable patch for bone regeneration as claimed in claim 4 or 5, wherein the solvent includes a group of Halogenated solvents comprising of Chloroform, Tetrachloro methane, Dichloro methane.

The process for preparation of nano fiber based osteo- conductive resorbable patch for bone regeneration as claimed in the claims 3-5, wherein the temperature during the process is 18-24°C.

The nano fiber based osteo-conductive resorbable patch for bone regeneration as claimed in any of the preceding claims 1-3 is applicable for repair of hollow bone defect such as cranium, maxillary sinus, spinal canal & palate etc. and containment of bone fragments, beta TCP / HA fillings.